Prevention and treatment of late complications after cranial radiation therapy

Childhood brain tumour survivors, particularly those treated with craniospinal radiotherapy, often pay a high price in the form of debilitating cognitive and other deficits. There are currently no treatments or preventive strategies available. The mechanisms revealed here provide opportunities to intervene and prevent, or even reverse, these deficits.

If we can reduce their injuries, we will not only improve quality of life of the survivors and their families, but also reduce the burden on society.Our multidisciplinary team works with distinct, yet synergistically overlapping, projects:1. Microglia are key modulators of inflammation after irradiation (IR).

Using single-cell RNA sequencing, we found that microglia are more affected than other cell types in the brain after IR, and that they drive the detrimental, inflammatory response over multiple phases.2. Lithium protects from injury and promotes regeneration, but doesn’t protect tumour cells.

We explore the mechanisms in multiple cell types and plan a randomised, placebo-controlled trial (LiBRA) with recruitment of 80 patients, starting August 2022.3.

Educational and occupational outcomes serve as ecologically valid parameters, complementing neuropsychological assessments, and we are pioneering efforts to use them to their full potential.